PhenX: Nutrition & Dietary SupplementsPhenX: Nutrition & Dietary Supplements Erin M. Ramos, PhD MPH...

38
PhenX: Nutrition & Dietary Supplements Erin M. Ramos, PhD MPH Office of Population Genomics NHGRI Joint Federal Agency Diet & -Omics Workshop, March 31, 2009

Transcript of PhenX: Nutrition & Dietary SupplementsPhenX: Nutrition & Dietary Supplements Erin M. Ramos, PhD MPH...

Page 1: PhenX: Nutrition & Dietary SupplementsPhenX: Nutrition & Dietary Supplements Erin M. Ramos, PhD MPH Office of Population Genomics NHGRI Joint Federal Agency Diet & -Omics Workshop,

PhenX: Nutrition & Dietary Supplements

Erin M. Ramos, PhD MPHOffice of Population GenomicsNHGRI

Joint Federal Agency Diet & -Omics Workshop, March 31, 2009

Page 2: PhenX: Nutrition & Dietary SupplementsPhenX: Nutrition & Dietary Supplements Erin M. Ramos, PhD MPH Office of Population Genomics NHGRI Joint Federal Agency Diet & -Omics Workshop,

NHGRI Office of Population Genomics Established to facilitate application of genomic

knowledge to health, by promoting multi-disciplinary research, applying genomic technologies to population and clinical studies, and developing new population resources for investigation of genetic and environmental contributions to complex diseases.

Goals: - Establish research resources to identify genes related to

complex diseases and their environmental modifiers - Build successful NIH-wide collaborations in population-based

genomics research- Support cross-disciplinary training for genetics, epidemiologist,

clinical researchers, and clinicians

http://www.genome.gov/19518660

Page 3: PhenX: Nutrition & Dietary SupplementsPhenX: Nutrition & Dietary Supplements Erin M. Ramos, PhD MPH Office of Population Genomics NHGRI Joint Federal Agency Diet & -Omics Workshop,

2007: The Year of GWA Studies

Pennisi E, Science 2007; 318:1842-43.

Page 4: PhenX: Nutrition & Dietary SupplementsPhenX: Nutrition & Dietary Supplements Erin M. Ramos, PhD MPH Office of Population Genomics NHGRI Joint Federal Agency Diet & -Omics Workshop,

200520062007 first quarter2007 second quarter2007 third quarter2007 fourth quarter2008 first quarter 2008 second quarter 2008 third quarter

Manolio, Brooks, Collins, J. Clin. Invest., May 2008

As of 12/30/08, > 281 publications on ~ 90 diseases/traits!

Page 5: PhenX: Nutrition & Dietary SupplementsPhenX: Nutrition & Dietary Supplements Erin M. Ramos, PhD MPH Office of Population Genomics NHGRI Joint Federal Agency Diet & -Omics Workshop,

(http://genome.gov/gwastudies)

Page 6: PhenX: Nutrition & Dietary SupplementsPhenX: Nutrition & Dietary Supplements Erin M. Ramos, PhD MPH Office of Population Genomics NHGRI Joint Federal Agency Diet & -Omics Workshop,

Standard Measures Needed Combining studies

increases ability to detect loci with moderate effect size (G x G; G x E interactions)

Once genome is characterized it can be related to any trait consistent with informed consent

Potential for cross-study analysis limited by lack of standardized measures

(www.broad.mit.edu/diabetes/scandinavs/type2.html)

Type 2 Diabetes GWAS (>380K SNPs)

Page 7: PhenX: Nutrition & Dietary SupplementsPhenX: Nutrition & Dietary Supplements Erin M. Ramos, PhD MPH Office of Population Genomics NHGRI Joint Federal Agency Diet & -Omics Workshop,

Standard Measures Needed Multi-IC Symposia on Applying Genomics Technologies

to Population Studies (2006)- Recommendations:

Limited subsets of phenotypic and exposure data that are amenable to common definition and standardized collection in GWAS should be identified in near future

Better methods for phenotyping (rigorous, standardized, inexpensive, non-invasive, limited burden, appropriate for asymptomatic individuals) are needed, particularly for phenotypes relevant to a wide variety of diseases and disabilities

Frontiers in Population Genomics (2007)- Recommendations:

Identify a subgroup of phenotypes and exposures with strong genetic associations for standardization and addition to GWAS

Support the review of phenotype and exposure data deposited in dbGaP to identify the most common measures and those that can be used in multiple studies.

Page 8: PhenX: Nutrition & Dietary SupplementsPhenX: Nutrition & Dietary Supplements Erin M. Ramos, PhD MPH Office of Population Genomics NHGRI Joint Federal Agency Diet & -Omics Workshop,

The PhenX Project (www.phenx.org) PI: Carol Hamilton (RTI)

Resource of established measures that can be incorporated into existing and future study protocols (e.g. GWAS and other genomic research efforts)

PhenX Toolkit will include 15 standardized measures for 20 research domains

Challenge: Selecting 15 measures that are low burden, but still useful

Page 9: PhenX: Nutrition & Dietary SupplementsPhenX: Nutrition & Dietary Supplements Erin M. Ramos, PhD MPH Office of Population Genomics NHGRI Joint Federal Agency Diet & -Omics Workshop,

PhenX Goals Select 15 low burden, useful measures for 20 research

domains- Domains are selected by the Steering Committee - Measures & protocols are chosen by expert Working Groups - Scientific community has the opportunity to review and comment on

initial set of 25 measures (via Web-based survey)

Final set of measures made available to the research community via the PhenX Toolkit - Ensure that their study will be compatible with others that also

incorporate PhenX measures- Combine studies to increase statistical power and the ability to

identify genes associated with complex diseases

Page 10: PhenX: Nutrition & Dietary SupplementsPhenX: Nutrition & Dietary Supplements Erin M. Ramos, PhD MPH Office of Population Genomics NHGRI Joint Federal Agency Diet & -Omics Workshop,

PhenX Domains (N=20) Alcohol, Tobacco, and Other

Substances* Anthropometrics* Cancer* Cardiovascular* Demographics* Diabetes Nutrition and Dietary

Supplements* Environmental Exposures* Gastrointestinal Infectious Disease and

Immunity

Lung Function Neurological Ocular Oral Health* Activity and Physical

Fitness Psychiatric Psychosocial Renal Function Reproduction Skin, Bone, Muscle, and

Joint

* In process or completed

Page 11: PhenX: Nutrition & Dietary SupplementsPhenX: Nutrition & Dietary Supplements Erin M. Ramos, PhD MPH Office of Population Genomics NHGRI Joint Federal Agency Diet & -Omics Workshop,

Process for selecting PhenX measures Criteria for measures:

- Low burden

- Good measurement properties

- Acceptable to the community

- Viable in the future

Can have more than 1 protocol- e.g. age-specific or gender

specific

Define scope of the domain

Identify broad list of measures

40 measures to SC

25 to Survey

15 to Toolkit

Page 12: PhenX: Nutrition & Dietary SupplementsPhenX: Nutrition & Dietary Supplements Erin M. Ramos, PhD MPH Office of Population Genomics NHGRI Joint Federal Agency Diet & -Omics Workshop,
Page 13: PhenX: Nutrition & Dietary SupplementsPhenX: Nutrition & Dietary Supplements Erin M. Ramos, PhD MPH Office of Population Genomics NHGRI Joint Federal Agency Diet & -Omics Workshop,

PhenX Toolkit Contents Recommended measures for each Domain

Detailed, standard protocols for collecting the measures

Methods to harmonize measures – as needed

Supporting documentation- Rationale for inclusion - References - Links to resources that include the measures (e.g., dbGaP)- Links to resources that provide in-depth information about additional

measures

Information about the measures – recognized standards, compatibility

Page 14: PhenX: Nutrition & Dietary SupplementsPhenX: Nutrition & Dietary Supplements Erin M. Ramos, PhD MPH Office of Population Genomics NHGRI Joint Federal Agency Diet & -Omics Workshop,

PhenX Nutrition and Dietary Supplements Working

Group (WG)

Page 15: PhenX: Nutrition & Dietary SupplementsPhenX: Nutrition & Dietary Supplements Erin M. Ramos, PhD MPH Office of Population Genomics NHGRI Joint Federal Agency Diet & -Omics Workshop,

Working Group Members Patrick Stover, PhD (Chair) Cornell University

Yvonne Bronner, ScD, RD Morgan State University

Cindy Davis, PhD National Cancer Institute

Johanna Dwyer, DSc, RD Tufts University / NIH

John P. Foreyt, PhD Texas Medical Center

Stephen Kritchevsky, PhD Wake Forest University

Anna Maria Siega-Riz, PhD University of North Carolina

Pamela Starke-Reed, PhD National Institutes of Health

Jose Ordovas, PhD (SC Liaison) Tufts University

Anne-Lynne McCalla, MPH, RD WG Manager, RTI International

Page 16: PhenX: Nutrition & Dietary SupplementsPhenX: Nutrition & Dietary Supplements Erin M. Ramos, PhD MPH Office of Population Genomics NHGRI Joint Federal Agency Diet & -Omics Workshop,

Working Group Timeline Introductory Call: 11/03/2008

Conference Call: 12/09/2008

In-person Meeting: 12/17/2008

Conference Call: 03/06/2009

Survey Launch: Spring, 2009

Tool Kit Release: Summer, 2009

Page 17: PhenX: Nutrition & Dietary SupplementsPhenX: Nutrition & Dietary Supplements Erin M. Ramos, PhD MPH Office of Population Genomics NHGRI Joint Federal Agency Diet & -Omics Workshop,

Initial Scope of the Domain Dietary components

- Vitamins, Minerals, Macro Nutrients

Food groups - dairy, fruits, vegetables, grains, fats,

alcohol, etc

Supplements- Multivitamins, single vitamins- Alternative supplements (e.g. soy,

gingko, fish oils)- Meal replacements (e.g. protein

bars)

Infant feeding- Breastfed - Formula- Introduction of solid foods

Food toxins- Endogenous (Mercury, PCBs)- Derived (Acrylamide, HCAs)

Away from home food consumption- Fast food, traditional

restaurants

Food sufficiency

Food preparation- Grilling- Frying- Microwaving, etc

Water

Page 18: PhenX: Nutrition & Dietary SupplementsPhenX: Nutrition & Dietary Supplements Erin M. Ramos, PhD MPH Office of Population Genomics NHGRI Joint Federal Agency Diet & -Omics Workshop,

Recommended Measures

Total Dietary Intake

Supplement Intake

Selenium

Vitamin D

Breast Feeding

Page 19: PhenX: Nutrition & Dietary SupplementsPhenX: Nutrition & Dietary Supplements Erin M. Ramos, PhD MPH Office of Population Genomics NHGRI Joint Federal Agency Diet & -Omics Workshop,

Studies & Instruments Reviewed

Black Women’s Health Study

Block Questionnaire

Behavioral Risk Factor Surveillance System

Questionnaire (BRFSS)

Daily Food Checklist

Diet History Questionnaire

Framingham Heart Study

Jackson Heart Study

National Health Interview

NHANES

Willett (Harvard Food Frequency) Questionnaire

Women’s Health Initiative

5-A-Day for Better Health

Page 20: PhenX: Nutrition & Dietary SupplementsPhenX: Nutrition & Dietary Supplements Erin M. Ramos, PhD MPH Office of Population Genomics NHGRI Joint Federal Agency Diet & -Omics Workshop,

Protocol Selection The WG considered pros & cons of various protocols:

- FFQ’s, 24 hour recall, Short Dietary Assessments (Screeners), Bioassays

The following protocols to be included in PhenX Survey:- 24 hour recall (Multiple Pass) for

Total Dietary Intake Supplement Intake

- Bioassay (NHANES laboratory protocol) for Selenium Vitamin D

- Short Dietary Assessment (NHANES questions) for Breast Feeding

Page 21: PhenX: Nutrition & Dietary SupplementsPhenX: Nutrition & Dietary Supplements Erin M. Ramos, PhD MPH Office of Population Genomics NHGRI Joint Federal Agency Diet & -Omics Workshop,

Short Dietary Assessments (Screeners)

Single and Multi-Factor including:- Fruits and Vegetables - Dairy- Added Sugars- Calcium - Fiber- Supplements- Caffeine

Page 22: PhenX: Nutrition & Dietary SupplementsPhenX: Nutrition & Dietary Supplements Erin M. Ramos, PhD MPH Office of Population Genomics NHGRI Joint Federal Agency Diet & -Omics Workshop,

PhenX Survey Survey is sent out to the larger research community

- Obtain opinions regarding the priority and appropriateness of the measures

- Assess the acceptability, feasibility, and usability of each of the measures

- Determine utility of the measurement protocols

Facilitate consensus, outreach, and acceptance of the priority measures

Your input welcome!

Page 23: PhenX: Nutrition & Dietary SupplementsPhenX: Nutrition & Dietary Supplements Erin M. Ramos, PhD MPH Office of Population Genomics NHGRI Joint Federal Agency Diet & -Omics Workshop,

Steering Committee MembersJonathan Haines, PhD (Chair)Vanderbilt University

William Harlan, MD (Vice Chair)National Library of Medicine

Terri Beatty, PhDJohns Hopkins School of Public Health

Lindsay Farrer, PhDBoston University

Peter Kraft, PhDHarvard School of Public Health

Mary Marazita, PhD, FACMGUniversity of Pittsburgh

Jose Ordovas, PhDTufts University

Erin Ramos, PhD, MPHNHGRI

Margaret Spitz, MD, MPHUniversity of Texas

Carlos Pato, MD, PhDUniversity of Southern Carolina

Diane Wagener, PhDRTI International

Michelle Williams, ScDUniversity of Washington

Page 24: PhenX: Nutrition & Dietary SupplementsPhenX: Nutrition & Dietary Supplements Erin M. Ramos, PhD MPH Office of Population Genomics NHGRI Joint Federal Agency Diet & -Omics Workshop,

NIH IC LiaisonsRichard Anderson (NIGMS)

Hemin Chin (NEI)

Elaine Collier (NCRR)

Kevin Conway (NIDA)

Emily Harris (NIDCR)

Anthony Hayward (NCRR)

John Ilekis (NICHD)

Mary E. Kerr (NINR)

Paul L. Kimmel (NIDDK)

Sue Krebs-Smith (NCI)

Jennie Larkin (NHLBI)

Thomas Lehner (NIMH)

James Luo (NIBIB)

John Lynch (NINDS)

Kimberly A. McAllister (NIEHS)

Jim Ostell (NLM)

Kyu Rhee (NCMHD)

Winifred K. Rossi (NIA)

Marcia Scott (NIAAA)

Kay Wanke (OBSSR)

Jim Witter (NIAMS)

Ashley Xia (NIAID)

Page 25: PhenX: Nutrition & Dietary SupplementsPhenX: Nutrition & Dietary Supplements Erin M. Ramos, PhD MPH Office of Population Genomics NHGRI Joint Federal Agency Diet & -Omics Workshop,

Acknowledgements OPG Colleagues

- Heather Junkins- Teri Manolio

SC Members WG Members IC Liaisons dbGaP

- Jim Ostell- Karl Sirotkin- Kim Tryka

RTI Colleagues- Carol Hamilton (PI)- Diane Wagener (Co-PI)- Tabitha Hendershot- Jane Hammond- Dean Jackman- Richard Kwok- Debbie Maiese- Destiney Nettles- Joe Pratt- Anne-Lyne McCalla- Survey Team- Web Team

Page 26: PhenX: Nutrition & Dietary SupplementsPhenX: Nutrition & Dietary Supplements Erin M. Ramos, PhD MPH Office of Population Genomics NHGRI Joint Federal Agency Diet & -Omics Workshop,

Websites www.phenx.org

- Register to receive periodic updates via e-mail of the PhenX Newsletter and notification of new surveys

www.phenxtoolkit.org- Additional domains and protocols will be added as they

become available

www.genome.gov/gwastudies/- A Catalog of Published Genome-Wide Association

Studies

Page 27: PhenX: Nutrition & Dietary SupplementsPhenX: Nutrition & Dietary Supplements Erin M. Ramos, PhD MPH Office of Population Genomics NHGRI Joint Federal Agency Diet & -Omics Workshop,

27

Page 28: PhenX: Nutrition & Dietary SupplementsPhenX: Nutrition & Dietary Supplements Erin M. Ramos, PhD MPH Office of Population Genomics NHGRI Joint Federal Agency Diet & -Omics Workshop,

28

What is a GWAS Method for interrogating all 10 million variable points across

human genome Variation inherited in groups, or blocks, so not all 10 million

points have to be tested Blocks are shorter (so need to test more points) the less

closely people are related Technology now allows studies in unrelated persons,

assuming 5,000 – 10,000 base pair lengths in common (300,000 – 1,000,000 markers)

Page 29: PhenX: Nutrition & Dietary SupplementsPhenX: Nutrition & Dietary Supplements Erin M. Ramos, PhD MPH Office of Population Genomics NHGRI Joint Federal Agency Diet & -Omics Workshop,

29

PhenX Definitions Domain

- field of research with a unifying theme and easily enumerated measures

- e.g. Alcohol, Tobacco, & Other Substance Use

Domain Element - group of measures and conditions that enclose similar assessments

and concepts- e.g. alcohol consumption, tobacco consumption, nicotine

dependence

Measure- refers broadly to a standardized way of capturing data on a certain

characteristic of or related to a study subject (including exposures, clinical assessments, and quantitative and qualitative traits )

- e.g. Fagerstrom Index to measure nicotine dependence

Page 30: PhenX: Nutrition & Dietary SupplementsPhenX: Nutrition & Dietary Supplements Erin M. Ramos, PhD MPH Office of Population Genomics NHGRI Joint Federal Agency Diet & -Omics Workshop,

30

Page 31: PhenX: Nutrition & Dietary SupplementsPhenX: Nutrition & Dietary Supplements Erin M. Ramos, PhD MPH Office of Population Genomics NHGRI Joint Federal Agency Diet & -Omics Workshop,

31

Page 32: PhenX: Nutrition & Dietary SupplementsPhenX: Nutrition & Dietary Supplements Erin M. Ramos, PhD MPH Office of Population Genomics NHGRI Joint Federal Agency Diet & -Omics Workshop,

32

Page 33: PhenX: Nutrition & Dietary SupplementsPhenX: Nutrition & Dietary Supplements Erin M. Ramos, PhD MPH Office of Population Genomics NHGRI Joint Federal Agency Diet & -Omics Workshop,

33

Page 34: PhenX: Nutrition & Dietary SupplementsPhenX: Nutrition & Dietary Supplements Erin M. Ramos, PhD MPH Office of Population Genomics NHGRI Joint Federal Agency Diet & -Omics Workshop,

34

Page 35: PhenX: Nutrition & Dietary SupplementsPhenX: Nutrition & Dietary Supplements Erin M. Ramos, PhD MPH Office of Population Genomics NHGRI Joint Federal Agency Diet & -Omics Workshop,

35

Substance Use Working Group Deborah Hasin, PhD (Chair) Columbia University

Laura Jean Bierut, MD Washington University in St. Louis

Kevin Conway, PhD National Institute on Drug Abuse

Jorge Delva, MSW, PhD University of Michigan

Richard Hayes, DDS, PhD National Cancer Institute

Victor M. Hesselbrock, PhD University of Connecticut

Mary Elizabeth O’Neil, MPH Working Group Manager RTI International

Marcia Scott, PhD National Institute on Alcohol Abuse

and Alcoholism

Robert E. Taylor, MD, PhD Howard University

Page 36: PhenX: Nutrition & Dietary SupplementsPhenX: Nutrition & Dietary Supplements Erin M. Ramos, PhD MPH Office of Population Genomics NHGRI Joint Federal Agency Diet & -Omics Workshop,

36

Substance Use Measures

Alcohol – lifetime use Alcohol – 30-day

quantity and frequency Alcohol – maximum

drinks in 24-hours Alcohol – age of first

use Tobacco – smoking

status Tobacco – 30-day

quantity and frequency Tobacco – age of

initiation of use

Tobacco – age of offset of use

Alcohol – lifetime dependence and abuse

Tobacco – nicotine dependence

Substances – lifetime abuse and dependence

Substances – lifetime use

Substances – 30-day frequency

Substances – age of first use

Page 37: PhenX: Nutrition & Dietary SupplementsPhenX: Nutrition & Dietary Supplements Erin M. Ramos, PhD MPH Office of Population Genomics NHGRI Joint Federal Agency Diet & -Omics Workshop,

37

Ethnicity

Page 38: PhenX: Nutrition & Dietary SupplementsPhenX: Nutrition & Dietary Supplements Erin M. Ramos, PhD MPH Office of Population Genomics NHGRI Joint Federal Agency Diet & -Omics Workshop,

38

Race